Process for the preparation of urea derivatives



Patented Aug. 17, 1937 UNITED STATES PATENT OFFICE PROCESS FOR THEPREPARATION OF UREA DERIVATIVES No Drawing. Application January 24,1936, Serial No. 60,705

12 Claims.

This invention relates to urea derivatives, more particularly to acyland aralkyl ureas, and to a process for the preparation thereof.

It is an object of this invention to provide a new and improved processfor producing substituted urea derivatives. A further object is theprovision of a new and improved process for the preparation of acylureas, that is, urea derivatives in which a hydrogen atom on one or bothof the urea nitrogen atoms is replaced by an acyl radical. A stillfurther object is the provision of a new and improved process forpreparing aralkyl ureas, that is, urea derivatives in which a hydrogenatom on one or both of the urea nitrogen is replaced by an aralkylgroup.

An additional object is the preparation of diureides by a new andimproved process. A more specific object is the provision of a new andimproved process for the synthesis of urea derivatives of the higherfatty acids. Another object is the preparation of new and usefulchemical compounds and compositions. Other objects will appearhereinafter.

In accomplishing these objects according to the present invention,substituted ureas are produced by reacting an alkali metal urea such as,for example, sodium urea, with an organic halide from the classconsisting of acyl and aralkyl halides. The alkali metal urea mayconvenient- 1y be obtained by reacting urea with a liquid ammoniasolution of the alkali metal in accordance with. methods described in myco-pending application Serial No. 15,425 filed April 9, 1935. Thereaction between the alkali metal urea and the acyl or aralkyl halidemay be effected by bringing these materials together at appropriatetemperatures in the presence or absence of diluents or solvents, suchas, for example, volatile organic solvents. The products may be isolatedand purified in any suitable manner, for instance, as hereinafterdescribed.

The process is preferably carried out by the direct reaction of theorganic halide with sodium urea, the latter being added slowly to theorganic halide in a liquid or fused state. Puriflcation' is preferablyeffected by dissolving the reaction product in a water-immisciblesolvent, extracting with water, and then separating the 50 solvent layercontaining the dissolved substituted urea from the water layer. Thesubstituted urea is usually recovered from the solution by evaporationof the solvent.

The invention will be further illustrated but ,55 is not limited by thefollowing examples in which the quantities are stated in parts byweight.

EXAMPLE I Oleul urea Stearyl urea This compound was synthesizedandpurified by the method described in Example I by mixing 2'7 parts ofsodium urea with 100 parts of stearyl chloride (stearic acid chloride)and allowing the mixture to stand overnight at room temperature.Analysis of the product obtained showed it to contain 8.24% nitrogen,whereas the calculated nitrogen content of monostearyl urea is 8.64%.

EXAMPLE III Benzoyl urea Twenty (20) parts of sodium urea were suspendedin 71.9 parts of ether, and 40 parts of benzoyl chloride were addedslowly, with stirring. The product was washed with water, filtered, andthen washed with ether. Fifteen (15) parts of product melting at 210-212C., and which was identified as benzoyl urea, were obtained.

EXAMPLE IV Phthalyl ureide Eight and two-tenths (8.2) parts of sodiumurea were added slowly, with gentle warming, to 10.3 parts of phthalylchloride, and 22 parts of benzene were then added to moderate thereaction. The benzene was evaporated, and the product crystallized fromalcohol. The melting point of the material obtained was 240 C. Thiscompound has the probable formula:

CONH\ co CONH/ Analysis showed it to contain 57.1% carbon, 3.2% hydrogenand 14.7% nitrogen, whereas the theoretical proportions of carbon,hydrogen and nitrogen in a compound of the above formula are 56.8%, 3.2%and 14.7%. respectively.

Exxuru: V

Benzyl urea A suspension of sodium urea in liquid ammonia wasflrstprepared by reacting 5.75 parts of sodium and 15 parts of urea inabout 312 Exxnrm VI Acetyl urea Sixty-two and five-tenths (62.5) partsof acetyl chloride were dissolved in an equal weight of toluene, thesolution refluxed, and then 82 parts of sodium urea added slowly insmall portions. Upon completion of the addition of the sodium urea, thesolution was allowed to cool, the sodium chloride filtered oil, and thefiltrate concentrated by evaporation until crystallization began. Theproduct purified by crystallization from hot ethyl alcohol wasidentified as acetyl urea.

EXAMPLE VII Dibenzoul urea To 10.4 parts of disodium urea, NaNHCONI-INa(prepared by the action of two moles of sodium upon one mole of the ureain liquid ammonia), were added slowly 28 parts of benzoyl chloride. Avigorous reaction took place. When this reaction subsided, the productwas crystallized from alcohol, and a white crystalline material meltingat 204 C. was obtained. It was identified as dibenzoyl urea by anitrogen analysis (calculated 10.44%; found 10.70%).

According to methods similar to those described in the examples, thereaction may be effected with any acyl or aralkyl halide. As examples ofacyl halides that are particularly useml in the practice of theinvention may be mentioned the halides of acids such as acetic,propionic, butyric, capric, caproic, decylic, undecylic, lauric,myristic, pentadecylic, palmitic, oleic, cerotic, abietic, phthalic,terephthalic, salicylic, mandelic, succinic, adipic, maleic, malonic,benzoic, phenyl acetic, toluic, naphthoic, and related acids. Theprocess is also applicable to the preparation of mixtures of substitutedureas, for example, such mixtures as are obtainable by the reaction ofsodium urea with the halides of fatty oil acid mixtures such as coconutoil acid chlorides or various fractions thereof, particularly thefractions in which lauric acid chloride preponderates. The lattercoconut oil acid fraction is herein referred to as "Lorol acid chloride.Similarly, there may be used in the process sperm oil acid halides andthe halides of those acid mixtures such as are obtainable by theoxidation of synthetic higher alcohol mixtures produced by thehydrogenation of carbon oxide. The latter type of acid mixture may beobtained, for example, by the oxidation of alcohol mixtures such asdescribed in Lawson, U. 8. Patent No. 2,015,077. The oxidation of thesealcohol mixtures may be carried out as described by Reid, U. 8. PatentNo. 1,856,263, or by catalytic oxidation, in the vapor phase, of, amixture of oxygenated organic compounds obtained in the catalyticsynthesis of methanol from carbon monoxide and hydrogen. The oxidationmay be eil'ected in the presence of of a suitable catalyst such as amanganese catalyst. The conversion of the free acids to the acidchlorides may be carried out by the usual method for convertingcarboxylic acids to the acid chlorides.

In general, the present process has given especially desirable resultsin the preparation of acyl ureas in which the acyl radical contains atleast eight carbon atoms, and particularly those containing eight toeighteen carbon atoms, inclusive.

As further examples oi aralkyl halides which may be employed inaccordance with the invention may be mentioned tolyl chloride, bensylfluoride, naphthyl chloride, 1:4-xylylene dichloride, trichlorobenzylchloride, and related compounds. In general, the preferred aralkylhalides may be given the formula:

where R is an aromatic radical (for instance, of the benzene,naphthalene or anthracene series), n is one or a number greater thanone, and x is halogen.

Generally speaking; the organic halides employed in accordance with theinvention may be chlorides, bromides, iodides or fluoridea, Thepractical utility of the invention is especially evidentin the case ofthe acyl and aralkyl chlorides.

The aromatic nuclei of the aralkyl halides and of the acyl halides ofaromatic carboxylic acids may contain substituents such as, for example,

halogen atoms, alkyl radicals (e. g., methyl, ethyl,v propyl and higherhomoiogues), and alkoxy radicals (e. g., methoxy, ethoxy, isopropoxy,n-butoxy, and higher homologues).

The proportions of the reacting materials may be varied according to thetype of compound reacted upon and the product desired. Thus, in order toproduce a ureide by reaction of a diacyl halide with, sodium urea,approximately equimolecular proportions of the reacting materials may beemployed. Likewise, monoacyl ureas are best secured by reactingmonosodium urea with the monoacyl halide inapproximately equimolecularproportions.

I have also found that certain aliphatic diureides (i. e., substitutedureas containing two -NHCONH: radicals) may be obtained by reacting analiphatic diacyl halide containing more than three carbon atoms with atleast two molecular proportions of sodium urea per mole of the aliphaticdiacyl halide.

Instead of sodium urea, other alkali metal tained at temperatures withinthe range of 40 C. when liquid ammonia is used to 75 C. when an organicdiluent such as benzene or toluene is used, but higher or lowertemperatures may be used. Generally, the time and temperature ofreaction will vary both with the method of preparation and the nature ofthe reacting ingredients. While it is usually preferable to carry outthe synthesis in the absence of a solvent, particularly with acyl andaralkyl halides which are normally liquid or which have relatively lowmelting points, in some cases it is desirable to carry out the reactionin the presence of an inert volatile organic solvent such as diethylether, petroleum ether, benzene, toluene, xylene and similar solvents.This latter method is especially useful in the treatment of high-meltingacyl or aralkyl halides.

The products of this invention may be employed in the synthesis ofresins of the urea-aldehyde type, which resins have important uses inthe coating and plastics arts; the lower acyl ureas, for example, aloneor in conjunction with urea, react readily with formaldehyde to formresinous bodies. The higher acyl ureas, such as stearyl urea, may beincorporated into a urea-aldehyde resin during or subsequent to itsformation, and its water-resistance and flexibility are therebyincreased. In general, the higher acyl ureas are useful for improvingthe water-resistance of synthetic resins or coating compositionscontaining them. In certain instances, the higher acyl ureas may be useddirectly as substitutes for natural waxes in the water-proofing ofpaper, wood and textiles.

The acyl and aralkyl ureas are also useful in the synthesis of rubberchemicals (e. g., accelerators, softeners, antioxidants), dispersing andwetting agents, flotation agents, parasiticides,

and dyes. For example, the higher acyl ureas,

upon sulfonation, are converted to valuable detergents.

The process of this invention is particularly advantageous in theproduction of acyl and aralkyl derivatives of urea which cannot bereadily prepared by procedures known heretofore. The present inventionis particularly useful in the synthesis of acyl ureas in which the acylgroup is that of a higher fatty acid, e. g., lauric acid,

stearic acid, and oleic acid. The process of this invention offers a.simple way for synthesizing ureides and diureides, by reaction of sodiumurea with acyl halides of polybasic acids.

As many apparently widely different embodiments of this invention may bemade without departing from the spirit and scope thereof, it is to beunderstood that I do not limit myself to the specific embodimentsthereof except as defined in the appended claims.

I claim:

1. In a process of producing substituted ureas, the step which comprisesreacting an alkali metal urea with an acyl halide.

2. In a process of producing acyl ureas, the step which comprisesreacting sodium urea with an acyl halide.

3. In a process of producing acyl ureas, the step which comprisesreacting sodium urea with an aromatic acyl halide.

4. In a process of producing acyl ureas, the step which comprisesreacting sodium urea with an acyl chloride.

5. In a process of producing acyl ureas, the

step which comprises reacting sodium urea with the chloride of amonocarboxylic acid.

6. In a process of producing acyl ureas, the step which comprisesreacting sodium urea with the chloride of a fatty acid.

7. In a process of producing acyl ureas, the step which comprisesreacting sodium urea with an acyl halide in the presence of an inertsolvent.

8. In a process of producing a ureide, the step which comprises reactingsodium urea with a urea, the step which comprises reacting sodium ureawith a normal straight chain acyl chloride containing from eight toeighteen carbon atoms in the acyl radical.

12. In a process of producing acyl ureas, the step which comprisesreacting sodium urea with stearic acid chloride.

RALPH A. JACOBSON.

